Cell “Self-Eating” (Autophagy) Mechanism in Alzheimer's Disease



The autophagy pathway is the major degradation pathway of the cell for long-lived proteins and organelles. Dysfunction of autophagy has been linked to several neurodegenerative disorders that are associated with an accumulation of misfolded protein aggregates. Alzheimer's disease, the most common neurodegenerative disorder, is characterized by 2 aggregate forms, tau tangles and amyloid-β plaques. Autophagy has been linked to Alzheimer's disease pathogenesis through its merger with the endosomal-lysosomal system, which has been shown to play a role in the formation of the latter amyloid-β plaques. However, the precise role of autophagy in Alzheimer's disease pathogenesis is still under contention. One hypothesis is that aberrant autophagy induction results in an accumulation of autophagic vacuoles containing amyloid-β and the components necessary for its generation, whereas other evidence points to impaired autophagic clearance or even an overall reduction in autophagic activity playing a role in Alzheimer's disease pathogenesis. In this review, we discuss the current evidence linking autophagy to Alzheimer's disease as well as the uncertainty over the exact role and level of autophagic regulation in the pathogenic mechanism of Alzheimer's disease. Mt Sinai J Med 77:59&–68, 2010. © 2010 Mount Sinai School of Medicine